3,4-Dichloro-1-(3-trifluoromethyl-phenyl)-pyrrole-2,5-dione | 39147-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 3,4-Dichloro-1-(3-trifluoromethyl-phenyl)-pyrrole-2,5-dione
• 英文别名: 3,4-Dichloro-1-[3-(trifluoromethyl)phenyl]pyrrole-2,5-dione
• CAS: 39147-10-9
• 化学式: C₁₁H₄Cl₂F₃NO₂
• 分子量: 310.059
• InChiKey: MALRBSBLPCUSNT-UHFFFAOYSA-N

物化性质

• 沸点：
  326.8±42.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-Dichloro-1-(3-trifluoromethyl-phenyl)-pyrrole-2,5-dione 在 mercury(II) diacetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 0.25h， 生成 6-(3-Trifluoromethyl-phenyl)-[1,3]dithiolo[5,6][1,4]dithiino[2,3-c]pyrrole-2,5,7-trione
  参考文献：
  名称：

  Hansen, Thomas K.; Varma, Sukumar K.; Edge, Stephen, Journal of the Chemical Society. Perkin transactions I, 1992, # 14, p. 1807 - 1810

  摘要：

  DOI：
• 作为产物：
  描述：

  2,3-二氯马来酸酐 、 间氨基三氟甲苯 在 sodium acetate 、 乙酸酐 作用下， 反应 2.0h， 生成 3,4-Dichloro-1-(3-trifluoromethyl-phenyl)-pyrrole-2,5-dione
  参考文献：
  名称：

  Thiazolidinone CFTR inhibitors with improved water solubility identified by structure–activity analysis

  摘要：

  The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator ( CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modi. cations in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with similar to 1 mu M CFTR inhibition potency and solubility >180 mu M(>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.044

文献信息

• WATER SOLUBLE SMALL MOLECULE INHIBITORS OF THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
  申请人：Verkman Alan S.

  公开号：US20110105565A1

  公开（公告）日：2011-05-05

  Provided herein are highly water soluble, thiazolidinone derivative compounds and glycine hydrazide derivative compounds that inhibit the ion transport activity of the cystic fibrosis transmembrane conductance regulator (CFTR). The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea. The compounds may also be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

  本文提供了高度水溶性的噻唑啉酮衍生物化合物和甘氨酸酰肼衍生物化合物，这些化合物抑制了囊性纤维化跨膜传导调节器（CFTR）的离子传输活性。本文描述的化合物和含有这些化合物的组合物对于治疗与CFTR活性异常增加相关的疾病、紊乱和疾病、紊乱和条件的后遗症非常有用，例如分泌性腹泻。这些化合物也可用于抑制或预防多囊肾病患者囊肿的扩张或形成。
• Thiazolidinone CFTR inhibitors with improved water solubility identified by structure–activity analysis
  作者：N.D. Sonawane、A.S. Verkman

  DOI：10.1016/j.bmc.2008.07.044

  日期：2008.9

  The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator ( CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modi. cations in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with similar to 1 mu M CFTR inhibition potency and solubility >180 mu M(>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease. (C) 2008 Elsevier Ltd. All rights reserved.
• Inhibition of Bfl-1 with N-aryl maleimides
  作者：John R. Cashman、Mary MacDonald、Senait Ghirmai、Karl J. Okolotowicz、Eduard Sergienko、Brock Brown、Xochella Garcia、Dayong Zhai、Russell Dahl、John C. Reed

  DOI：10.1016/j.bmcl.2010.09.046

  日期：2010.11

  High-throughput screening of 66,000 compounds using competitive binding of peptides comprising the BH3 domain to anti-apoptotic Bfl-1 led to the identification of 14 validated 'hits' as inhibitors of Bfl-1. N-Aryl maleimide 1 was among the validated 'hits'. A chemical library encompassing over 280 analogs of 1 was prepared following a two-step synthesis. Structure-activity studies for inhibition of Bfl-1 by analogs of N-aryl maleimide 1 revealed a preference for electron-withdrawing substituents in the N-aryl ring and hydrophilic amines appended to the maleimide core. Inhibitors of Bfl-1 are potential development candidates for anti-cancer therapeutics. (C) 2010 Elsevier Ltd. All rights reserved.
• Hansen, Thomas K.; Varma, Sukumar K.; Edge, Stephen, Journal of the Chemical Society. Perkin transactions I, 1992, # 14, p. 1807 - 1810
  作者：Hansen, Thomas K.、Varma, Sukumar K.、Edge, Stephen、Charlton, Adam、Underhill, Allan E.、Becher, Jan

  DOI：——

  日期：——